ARDS and aging: TYMS emerges as a promising biomarker and therapeutic target.

Background: Acute Respiratory Distress Syndrome (ARDS) is a common condition in the intensive care unit (ICU) with a high mortality rate, yet the diagnosis rate remains low. Recent studies have increasingly highlighted the role of aging in the occurrence and progression of ARDS. This study is committed to investigating the pathogenic mechanisms of cellular and genetic changes in elderly ARDS patients, providing theoretical support for the precise treatment of ARDS. Methods: Gene expression profiles for control and ARDS samples were obtained from the Gene Expression Omnibus (GEO) database, while aging-related genes (ARGs) were sourced from the Human Aging Genomic Resources (HAGR) database. Differentially expressed genes (DEGs) were subjected to functional enrichment analysis to understand their roles in ARDS and aging. The Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning pinpointed key modules and marker genes, with ROC curves illustrating their significance. The expression of four ARDS-ARDEGs was validated in lung samples from aged mice with ARDS using qRT-PCR. Gene set enrichment analysis (GSEA) investigated the signaling pathways and immune cell infiltration associated with TYMS expression. Single-nucleus RNA sequencing (snRNA-Seq) explored gene-level differences among cells to investigate intercellular communication during ARDS onset and progression. Results: ARDEGs are involved in cellular responses to DNA damage stimuli, inflammatory reactions, and cellular senescence pathways. The MEmagenta module exhibited a significant correlation with elderly ARDS patients. The LASSO, RRF, and XGBoost algorithms were employed to screen for signature genes, including CKAP2, P2RY14, RBP2, and TYMS. Further validation emphasized the potential role of TYMS in the onset and progression of ARDS. Immune cell infiltration indicated differential proportion and correlations with TYMS expression. SnRNA-Seq and cell-cell communication analysis revealed that TYMS is highly expressed in endothelial cells, and the SEMA3 signaling pathway primarily mediates cell communication between endothelial cells and other cells. Conclusion: Endothelial cell damage associated with aging could contribute to ARDS progression by triggering inflammation. TYMS emerges as a promising diagnostic biomarker and potential therapeutic target for ARDS.

Analysis of Factors Influencing the Duration of Early Enteral Nutrition Support in Patients Diagnosed with Acute Pancreatitis.

Objective: This study aimed to assess the current status of early enteral nutrition (EN) support among patients diagnosed with acute pancreatitis (AP) and analyze the factors influencing its duration. The findings aimed to provide guidance for the development of tailored EN support protocols for pancreatitis patients. Methods: A convenience sampling method was employed, and 51 patients diagnosed with acute pancreatitis (AP) were enrolled from the Gastroenterology Department of Zhoushan Hospital between May 2020 and June 2021. Data analysis included the categorization of patients based on their early enteral nutrition (EN) support duration, followed by thorough statistical analysis, including logistic regression, to identify the factors impacting EN duration. Results: The mean duration of early EN support among AP patients was (93.57 ± 43.29) hours. A mere 13.73% of patients initiated EN within 48 hours of admission. Upon categorizing patients by the median duration of EN support, multiple logistic regression analysis revealed several significant risk factors influencing the duration of EN in AP patients, including patient age, underlying medical conditions, severity of pancreatitis, nutritional status, and blood lipase levels (P < .05). Conclusion: The study highlights the significant influence of disease severity and patients' functional status on the duration of early EN support in AP cases. It emphasizes the importance of a comprehensive patient assessment by medical professionals to determine the optimal timing for initiating EN support.

Gardenia jasminoides J. Ellis extract attenuates memory impairment in rats with Alzheimer's disease by suppressing NLRP3 inflammasome.

Alzheimer's disease (AD) is characterized by degeneration of the central nervous system. Recently, many studies have emphasized the beneficial role of Gardenia jasminoides J. Ellis extract (GJ-4) in neuroprotection, which is considered a potential drug for treating AD. However, the mechanism underlying its neuroprotective effects is obscure. This research intended to analyze the effectiveness of GJ-4 to induce neuronal protective role on a rat model of neurotoxicity and probe the potential mechanism. An AD model was established by intraperitoneal injection of aluminum chloride (AlCl3). Then, AlCl3-induced rats were administered 25 mg/kg and 50 mg/kg of GJ-4 orally. This study indicated that GJ-4 (25 and 50 mg/kg) mitigated AD-like behaviors, as evidenced by enhanced ambulation frequency, rearing frequency, and time spent in the target quadrant and decreased grooming frequency, defecation frequency, and escape latency in AlCl3-challenged rats. Also, GJ-4 at 25 and 50 mg/kg exerted an anti-apoptosis effect in the hippocampus of AlCl3-treated rats. Furthermore, GJ-4 (25 and 50 mg/kg) exhibited an anti-inflammatory effect in the hippocampus by repressing the activation of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, further inhibiting the activation of Caspase 1, ASC, IL-1ß, and IL-18 in AD hippocampus. Altogether, GJ-4 mitigated AlCl3-triggered impairment of learning and memory in AD rats via repressing NLRP3 inflammasome.

Efficacy and safety of gastroscopic hemostasis in the treatment of acute gastric hemorrhage: A meta-analysis.

BACKGROUND: Gastric cancer (GC) is a malignant tumor with a high incidence and mortality rate worldwide for which acute bleeding is a common clinical complication. Gastroscopic hemostasis is an important method for treating acute bleeding in GC; however, its efficacy and safety remain controversial. AIM: To systematically analyze the efficacy and safety of gastroscopic hemostasis for the treatment of acute gastric hemorrhage. METHODS: The PUBMED, Web of Science, Wiley Library, EMBASE, Wanfang, CNKI, and VIP databases were searched for studies related to gastroscopic hemostatic treatment for acute GC published through February 20, 2023. The literature was screened according to the inclusion and exclusion criteria, data were extracted, and literature quality was evaluated. The meta-analysis was performed using RevMan software (version 5.3), while Begg's test for publication bias was performed using Stata 13.0 software. RESULTS: Six randomized controlled trials and two retrospective analyses were retrieved. Five studies had a low, two had an uncertain, and one had a high risk of bias. Compared with the control group, the hemostatic rate of gastroscopic hemostasis was increased [relative risk (RR) = 1.24; 95% confidence interval (CI): 1.08 to 1.43; P = 0.003]; the rate of rebleeding (RR = 0.27; 95%CI: 0.09 to 0.80; P = 0.02), rate of surgery transfer (RR = 0.16; 95%CI: 0.06 to 0.43; P = 0.0003), serum C-reactive protein level [mean difference (MD) = -5.16; 95%CI: -6.11 to 4.21; P < 0.00001], interleukin-6 level (MD = -6.37; 95%CI: -10.33 to -2.42; P = 0.002), and tumor necrosis factor-α level (MD = -2.29; 95%CI: -4.06 to -0.52; P = 0.01) were decreased; and the quality of life improvement rate was increased (RR = 1.95; 95%C I= 1.41-2.71; P < 0.0001). Begg's test revealed no significant publication bias. CONCLUSION: The efficacy and safety of endoscopic hemostasis were higher than those of the control group, suggesting that it is an effective treatment for acute GC hemorrhage.

Impact of the cytotoxic T-lymphocyte associated antigen-4 rs231775 A/G polymorphism on cancer risk.

Background: Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is an immunosuppressive checkpoint that is involved in the development and metastasis of cancers. Several studies revealed that CTLA-4 rs231775A/G polymorphism may be associated with the risk of cancer in some populations, but the conclusions of these studies are not consistent. Methods: We conducted a pooled analysis with eligible studies to explore the association between the CTLA-4 rs231775 variant and cancer risk. Additionally, we used in silico tools to evaluated the expression of CTLA-4 on urinary system cancer. Moreover, we adopted the enzyme-linked immunosorbent assay (ELISA), and Gene Set Enrichment Analysis (GSEA) to investigate the effects of CTLA-4 on bladder cancer (BLCA). Results: In total, 92 case-control studies involving 29,987 patients with cancer and 36,484 healthy individuals (controls) were included in the pooled analysis. In the stratified analysis based on cancer type, the rs231775 A/G polymorphism was associated with increased bladder cancer risk in the heterozygote contrast model (OR = 1.23, 95% CI = 1.01-1.51, P = 0.040). The race-stratified analysis revealed that East Asians with the GG genotype had a 12% lower risk of developing cancer than those with the GA + AA genotype (95% CI = 0.81-0.95, P = 0.001). The in silico analysis showed that CTLA-4 expression was augmented in patients with BLCA. The ELISA results revealed that CTLA-4 expression was reduced in patients with BLCA carrying the AA genotype. Several signaling pathways, including cytokine-cytokine receptor interactions and T-cell receptor signaling, were associated with CTLA-4 expression. Conclusion: The CTLA-4 rs231775 A/G polymorphism is associated with cancer risk in East Asian population. This polymorphism is especially associated with BLCA.

Global, regional, and national burden of neurological disorders in 204 countries and territories worldwide.

Background: We aimed to determine the incidence and disability-adjusted life-years (DALYs) of neurological disorders worldwide from 1990 to 2019. Methods: We obtained age-standardised incidence and DALY rates of neurological disorders in 204 countries and territories from 1990 to 2019 from the Global Burden of Disease (GBD) database. We determined trends stratified by age, sex, region, country, and Social Development Index (SDI) and the risk factors contributing to DALYs associated with these neurological disorders. Results: The largest increases in the age-standardised incidence rates of neurological disorders in 1990-2019 occurred in four regions (East Asia: estimated annual percentage change (EAPC) = 0.19, tropical Latin America: EAPC = 0.07, Southern Latin America: EAPC = 0.03, Western Europe: EAPC = 0.03) and three countries (China: EAPC = 0.20, Ecuador: EAPC = 0.13, Italy: EAPC = 0.13). We observed the largest increases in age-standardised incidence rates for Parkinson disease, idiopathic epilepsy, and bipolar disorder, and in age-standardised DALY rates for Alzheimer disease and other dementias. High-SDI regions showed the highest EAPC for age-standardised incidence rates of Parkinson disease, depression, and motor neuron disease, and age-standardised DALY rates of neurological disorders. Conclusions: There is a need to control the increase in age-standardised incidence rates of neurological disorders in East Asia, tropical Latin America, Southern Latin America, and Western Europe, particularly in China, Ecuador, and Italy.

Red Tide Detection Method Based on Improved U-Net Model-Taking GOCI Data in East China Sea as an Example.

In the coastal areas of China, the eutrophication of seawater leads to the continuous occurrence of red tide, which has caused great damage to Marine fisheries and aquatic resources. Therefore, the detection and prediction of red tide have important research significance. The rapid development of optical remote sensing technology and deep-learning technology provides technical means for realizing large-scale and high-precision red tide detection. However, the difficulty of the accurate detection of red tide edges with complex boundaries limits the further improvement of red tide detection accuracy. In view of the above problems, this paper takes GOCI data in the East China Sea as an example and proposes an improved U-Net red tide detection method. In the improved U-Net method, NDVI was introduced to enhance the characteristic information of the red tide to improve the separability between the red tide and seawater. At the same time, the ECA channel attention mechanism was introduced to give different weights according to the influence of different bands on red tide detection, and the spectral characteristics of different channels were fully mined to further extract red tide characteristics. A shallow feature extraction module based on Atrous Spatial Pyramid Convolution (ASPC) was designed to improve the U-Net model. The red tide feature information in a multi-scale context was fused under multiple sampling rates to enhance the model's ability to extract features at different scales. The problem of limited accuracy improvement in red tide edge detection with complex boundaries is solved via the fusion of deep and shallow features and multi-scale spatial features. Compared with other methods, the method proposed in this paper achieves better results and can detect red tide edges with complex boundaries, and the accuracy, precision, recall, and F1-score are 95.90%, 97.15%, 91.53%, and 0.94, respectively. In addition, the red tide detection experiments in other regions with relatively concentrated distribution also prove that the method has good applicability.

Baicalein promotes the microglia M2 polarization and suppresses apoptosis by targeting HMOX1/PDE4D to alleviate Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that has quickly becoming one of the most expensive, lethal, and burdening diseases of this century. In the past twenty years, hundreds of drugs have been tested while only several have been authorized by FDA for AD treatment, hence, searching for candidate agent with therapeutic potential for AD is imminent. Controlling polarization direction of microglia is crucial in AD therapy. Recent research suggests that baicalein has potential to reduce neuroinflammation and prevent neurodegenerative diseases by affecting microglia, while the specific molecular mechanism of baicalein in regulating microglia in the treatment of AD is still unclear. In this study, we investigated how baicalein affected microglial polarization in AD and potential biological mechanisms. In cell experiments, it was verified that baicalein significantly shifted the BV-2 microglia phenotype from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, inhibited the microglial apoptosis and pro-inflammatory factors, promoted the microglial Aß uptake and anti-inflammatory factors after LPS stimulated. In APP/PS1 mice, it was found that baicalein decreased the Aß plaque deposition in brain, attenuated NLRP3 inflammasome activation and neuronal apoptosis in APP/PS1 mice. Furthermore, bioinformatics analysis and experiment validated that HMOX1 is a target of baicalein, and we elucidated that baicalein modulated the microglial polarization to inhibit neuroinflammation and neural injury through targeting on the HMOX1/PDE4D axis in AD. In conclusion, our findings indicate the therapeutic effect of baicalein for AD, and baicalein might serve a potential agent for AD treatment.

A cross-sectional survey on mother-to-child transmission of HIV among the migrant population in Dongguan, China.

Introduction: The migrant population, consisting of individuals who relocate from rural to urban areas, faces unique challenges that heighten their vulnerability to HIV infection. These challenges stem from a combination of sociodemographic factors and limited access to healthcare services. Understanding the dynamics of HIV transmission within this population is crucial for the development of effective prevention strategies. Methods: To investigate the factors contributing to HIV vulnerability among migrants, we conducted a cross-sectional study at Dongguan People's Hospital from January 1, 2018, to December 31, 2021. Our study focused on pregnant women living with HIV and their infants, with a particular emphasis on sociodemographic characteristics, HIV testing and treatment profiles, and neonatal clinical data. Data were systematically collected using standardized forms. Results: Analysis of data from 98 participants revealed noteworthy findings. No significant associations were observed between age, marital status, and educational background regarding HIV vulnerability. Similarly, factors such as the status of sexual partners, spousal therapy, and the number of children had no significant impact. However, our analysis highlighted the critical role of treatment strategies for HIV-positive women and the timing of antiretroviral therapy initiation for women with HIV, both of which were associated with HIV transmission (P < 0.05). Additionally, factors such as feeding type, neonatal antiretroviral prophylaxis, and preventive treatment strategies showed significant associations, while the preventive treatment program for neonates demonstrated no significant impact. Discussion: These findings provide valuable insights into the specific risk factors and barriers to HIV prevention faced by the migrant population in Dongguan. They underscore the importance of targeted interventions and policies aimed at curtailing mother-to-child HIV transmission. By addressing the unique challenges experienced by migrant mothers and their infants, this study contributes significantly to broader efforts in controlling the spread of HIV, ultimately enhancing the health outcomes and well-being of Dongguan's migrant population. Furthermore, our research introduces a distinctive perspective within the extensively examined domain of Prevention of Mother-to-Child Transmission (PMTCT) programs, focusing on the internally migrant Chinese population, an understudied demographic group in this context. This study, conducted in Dongguan, China, represents one of the pioneering investigations into pregnant women with HIV and their infants within this migrant community.

A Bayesian network perspective on neonatal pneumonia in pregnant women with diabetes mellitus.

OBJECTIVE: To predict the influencing factors of neonatal pneumonia in pregnant women with diabetes mellitus using a Bayesian network model. By examining the intricate network connections between the numerous variables given by Bayesian networks (BN), this study aims to compare the prediction effect of the Bayesian network model and to analyze the influencing factors directly associated to neonatal pneumonia. METHOD: Through the structure learning algorithms of BN, Naive Bayesian (NB), Tree Augmented Naive Bayes (TAN), and k-Dependence Bayesian Classifier (KDB), complex networks connecting variables were presented and their predictive abilities were tested. The BN model and three machine learning models computed using the R bnlean package were also compared in the data set. RESULTS: In constraint-based algorithms, three algorithms had different presentation DAGs. KDB had a better prediction effect than NB and TAN, and it achieved higher AUC compared with TAN. Among three machine learning modes, Support Vector Machine showed a accuracy rate of 91.04% and 67.88% of precision, which was lower than TAN (92.70%; 72.10%). CONCLUSION: KDB was applicable, and it can detect the dependencies between variables, identify more potential associations and track changes between variables and outcome.

The global landscape of bladder cancer incidence and mortality in 2020 and projections to 2040.

Background: Bladder cancer (BCa) is one of the most common urological malignancies worldwide. This study examines the global epidemiological profile of BCa incidence and mortality in 2020 and the projected burden to 2040. Methods: The estimated number of BCa cases and deaths were extracted from the GLOBOCAN 2020 database. Age-standardised incidence rates (ASIRs) and age-standardised mortality rates (ASMRs) were calculated using the world standard. The predicted BCa incidence and mortality in 2040 was calculated based on demographic projections. Results: Globally, approximately 573 000 new BCa cases and 213 000 deaths occurred in 2020, corresponding to ASIRs and ASMRs of 5.6 and 1.9 per 100 000, respectively. The incidence and mortality rates were approximately 4-fold higher in men (9.5 and 3.3 per 100 000, respectively) than women (2.4 and 0.9, respectively). Across world regions, incidence rates varied at least 12-fold among men and 8-fold among women, with the highest ASIRs for both men and women detected in Southern Europe (26.5 and 5.8 per 100 000, respectively) and Western Europe (21.5 and 5.8, respectively) and the lowest in Middle Africa (2.2) in men and South-Central Asia (0.7) in women. The highest ASMRs for both men and women were found in Northern Africa (9.2 and 1.8 per 100 000, respectively). By 2040, the annual number of new BCa cases and deaths will increase to 991 000 (72.8% increase from 2020) and 397 000 (86.6% increase), respectively. Conclusions: Geographical distributions of BCa incidence and mortality uncovered higher risk of BCa incidence in Southern and Western European populations and higher risk of mortality in Northern African populations. Considering the predicted 73% and 87% increase in annual BCa cases and deaths by 2040 globally, respectively, there is an urgent need to develop and accelerate BCa control initiatives for high-risk populations to tackle global BCa burden and narrow its geographical disparities.

Erector spinae plane block for pain control after hip surgeries: A systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to generate collated evidence on the efficacy of erector spinae plane block (ESPB) for pain control after hip surgeries. METHODS: All randomized controlled trials (RCTs) published on the databases of PubMed, CENTRAL, Embase, Web of Science, Google Scholar, and Open Gray up to 4 March 2023 and comparing ESPB with placebo for pain control after hip surgeries were eligible for inclusion. RESULTS: We included five RCTs. Meta-analysis showed that ESPB significantly reduced pain scores at 1 h (mean difference [MD]: -1.04; 95% confidence interval [CI]: -1.69, -0.40; I2 = 35%; p = 0.01), 3 h (MD: -0.95; 95% CI: -1.86, -0.03; I2 = 78%; p = 0.04), and 6 h (MD: -0.94; 95% CI: -1.77, -0.10; I2 = 73%; p = 0.03). However, no difference was noted for 12 h (MD: -0.33; 95% CI: -2.20, 1.53; I2 = 97%; p = 0.73) and 24 h pain scores (MD: 0.05; 95% CI: -0.58, 0.68; I2 = 71%; p = 0.87); 24 h total opioid consumption was not significantly different with ESPB and placebo (MD: -9.26; 95% CI: -24.49, 5.98; I2 = 94%; p = 0.23). CONCLUSION: Scarce evidence shows that ESPB may not provide adequate pain control after hip surgeries. No difference in 24-h pain scores and total opioid consumption was noted between ESPB and placebo. Further RCTs shall strengthen available evidence.

Viral hepatitis increases the risk of cholangiocarcinoma: a systematic review and meta-analysis.

Background: Whether viral hepatitis increases the risk of cholangiocarcinoma (CCA) has been controversial. The reasons for the differences between previous research results may be related to the differences in sample size, region, living environment and course of disease. A meta-analysis is needed to clarify the correlation between them and select the key population for early screening of CCA. Meta-analysis was used to explore the relationship between viral hepatitis and the risk of CCA, so as to provide evidence for the prevention and treatment of CCA. Methods: We systematically searched EmBase, SinoMed, PubMed, Web of Science China National Knowledge Infrastructure, and Wanfang databases. The quality of the included literature was evaluated using the Newcastle Ottawa Scale. Before merging the effect quantities, the data was first subjected to heterogeneity testing. Heterogeneity testing was evaluated using I2 (the proportion of heterogeneity variation to overall variation). Subgroup analysis was used to identify sources of heterogeneity in this study. The effect odds ratio (OR) of various studies was extracted or calculated for consolidation. Beta's rank correlation, Egger's Law of Return and funnel plot were used to test publication bias. Conduct subgroup analysis based on the regions included in the literature. Results: A total of 2,113 articles were retrieved, and a total of 38 articles were included in the meta-analysis. There are 29 case-control studies and 9 Cohort study, including 333,836 cases and 4,042,509 controls. The combined risk estimate of all studies showed a statistically significant increased risk of CCA, extrahepatitis and intrahepatitis incidence with hepatitis B virus (HBV) infection (OR =1.75, OR =1.49, and OR =2.46, respectively). The combined risk estimate of all studies showed a statistically significant increased risk of CCA, extrahepatitis and intrahepatitis incidence with hepatitis C virus (HCV) infection (OR =1.45, OR =2.00, and OR =2.81, respectively). The research points of HCV and CCA were asymmetric, indicating that there may be publication bias in the study of HCV and CCA. Conclusions: HBV and HCV infection could increase the risk of CCA. Therefore, in clinical practice, attention should be paid to CCA screening and early prevention of HBV and HCV infected patients.

Comparison of microsurgical clipping with intravascular interventional embolization in the treatment of ruptured aneurysms and risk factors for intraoperative rupture and bleeding.

OBJECTIVE: To investigate the effectiveness of microsurgical clipping compared with intravascular interventional embolization in the treatment of ruptured aneurysms and the risk factors for intraoperative rupture and bleeding. METHODS: The data of 116 patients with ruptured aneurysms admitted to the People's Hospital of China Three Gorges University from January 2020 to March 2021 were collected for retrospective analysis. Among them, 61 cases with microsurgical clipping were classified as the control group (CG), and the rest 55 with intravascular interventional embolization were the observation group (OG), and the treatment effects in the two groups were compared. The general conditions of operation (operation time, postoperative hospital stay and intraoperative blood loss) were compared between the two groups. The intraoperative rupture of cerebral aneurysm during operation was counted, and the incidence of complications between the groups was compared. Risk factors affecting intraoperative rupture of cerebral aneurysms were analyzed by logistic regression. RESULTS: The total clinical treatment efficiency was dramatically higher in the OG than that in the CG (P<0.05). The operative time, postoperative hospital stays, and intraoperative bleeding were all higher in the CG than those in the OG (all P<0.001). There was no statistical difference in the incidence of wound infection, hydrocephalus, and cerebral infarction between the two groups (all P>0.05). However, the incidence of intraoperative rupture was markedly higher in the CG than that in the OG (P<0.05). Multifactorial logistic regression analysis revealed that history of subarachnoid hemorrhage, history of hypertension, large diameter of aneurysm, irregular morphology, and anterior communicating artery aneurysm were independent risk factors for intraoperative rupture in patients. CONCLUSION: Intravascular interventional embolization for middle cerebral artery aneurysm rupture is a less invasive procedure with faster recovery time, and history of subarachnoid hemorrhage, history of hypertension, large diameter of aneurysm, irregular morphology, and anterior communicating artery aneurysm are independent risk factors affecting patients with intraoperative rupture.

Flower-like Cu9S8 nanocatalysts with highly active sites for synergistic NIR-II photothermal therapy and chemodynamic therapy.

Chemodynamic therapy (CDT) is a promising reactive oxygen species-based therapeutic strategy for tumor therapy. However, the poor reaction kinetics of CDT agents severely restricts its further application. Herein, protamine stabilized flower-like Cu9S8 (PS@Cu9S8) nanocatalysts are fabricated via a one-pot biomineralization strategy for synergistic second near-infrared (NIR-II) photothermal therapy (PTT) and CDT of tumor. The PS@Cu9S8 nanocatalysts possess a high surface area (40.10 m2 g-1), which is higher than those of the previously reported solid and hollow copper sulfide nanoparticles. The high surface area of PS@Cu9S8 nanocatalysts increases the number of active sites during the Fenton-like reaction, thereby accelerating the efficiency of CDT. Meanwhile, the PS@Cu9S8 nanocatalysts show a high extinction coefficient (21.41 L g-1 cm-1) and photothermal conversion efficiency (42.34%), which results in an outstanding PTT efficiency and facilitate ˙OH generation for CDT. Furthermore, RNA-sequencing unveils the whole-genome expression change of 4T1 cells after PS@Cu9S8 nanocatalyst treatment, revealing the apparent changes in ROS, cell cycle, and apoptosis-related pathways. In vivo experiments proved the good therapeutic efficiency and negligible systematic toxicity of PS@Cu9S8 nanocatalysts. This work not only develops a superior multifunctional nanocatalyst for synergistic PTT and CDT of tumor, but also provides a facile approach to construct high-performance agents for cancer therapy.

Development and assessment of the Quality of Life Instruments for Chronic Diseases-Gout (QLICD-GO) (V2.0).

OBJECTIVE: To develop and assess the Quality of Life Instruments for Chronic Diseases-Gout QLICD-GO (V2.0). METHODS: The instrument was developed using a programmatic decision-making method to combine the general module of the Quality of Life Instruments for Chronic Diseases and a new specific module. The instrument was assessed by measuring the quality of life of 116 patients with gout. RESULTS: The QLICD-GO (V2.0) included 28 items from the general module of chronic diseases and 12 items in three facets from the specific module. In addition to the field of physiological function, the internal consistency reliability of other fields and dimensions of the instrument was > 0.7, and the split-half reliability was > 0.5. Three common factors were extracted from the specific module, with a cumulative variance contribution rate of 57.54%. The standardized response means of the specific module and the whole instrument were 0.94 and 1.20, respectively. CONCLUSIONS: The QLICD-GO (V2.0) has good reliability, validity, and responsiveness. The instrument comprehensively and objectively reflects the quality of life of patients with gout, and it can be used to assess treatment regimens developed by medical staff. Key Points • The QLICD-GO (V2.0) has been developed for patients with gout based upon the foundation of the QLICD-GM. • The QLICD-GO reflects the clinical signs and symptoms, drug-related side effects, and psychological changes specific to patients with gout. • Based on the assessment results, the QLICD-GO (V2.0) has good reliability, validity, and responsiveness. • QLICD-GO (V2.0) can objectively and comprehensively reflect the QOL of patients with gout and can be used by clinical staff to assess treatment regimens.

In Situ Biosynthesis of Photothermal Parasite for Fluorescence Imaging-Guided Photothermal Therapy of Tumors.

Photothermal therapy (PTT) has been widely known as a promising therapeutic strategy for cancer treatment in recent decades. However, some organic and inorganic photothermal agents exhibit shortcomings including potential long-term toxicity and lack of biodegradability. Biocompatible extracts from plants and animals provide several alternatives for the reformation of photothermal agents. Bio-inspired products still have inherent problems such as low accumulation in tumors, easy diffusion, and fast elimination. Herein, we aim to develop a biocompatible photothermal agent with tumor enrichment. Enlightened by "parasitized snails", in situ biosynthesis of photothermal agents and fluorescence imaging-guided PTT are achieved with the assistance of alginate-calcium-genipin (ACG) hydrogel. ACG hydrogel is a mixture of alginate (ALG), calcium (Ca), and genipin (GP). Given that the crosslinking product of GP and protein displays fluorescent/photothermal features, the constructed ACG hydrogel can gradually react with the tumor and then "light up" and "ignite" the tumor under specific light excitation. The ACG hydrogel can be seen as a photothermal parasite, eventually leading to the death of tumor. The photothermal therapeutic effects of ACG hydrogel reacting with tumors are successfully proven in vivo. The naturally derived GP and ALG ensure the biosafety of the ACG hydrogel-based bio-application. This work is another successful practice of nature-inspired methodological strategy for in situ biosynthesis of the photothermal agent.

Classification of Building Damage Using a Novel Convolutional Neural Network Based on Post-Disaster Aerial Images.

The accurate and timely identification of the degree of building damage is critical for disaster emergency response and loss assessment. Although many methods have been proposed, most of them divide damaged buildings into two categories-intact and damaged-which is insufficient to meet practical needs. To address this issue, we present a novel convolutional neural network-namely, the earthquake building damage classification net (EBDC-Net)-for assessment of building damage based on post-disaster aerial images. The proposed network comprises two components: a feature extraction encoder module, and a damage classification module. The feature extraction encoder module is employed to extract semantic information on building damage and enhance the ability to distinguish between different damage levels, while the classification module improves accuracy by combining global and contextual features. The performance of EBDC-Net was evaluated using a public dataset, and a large-scale damage assessment was performed using a dataset of post-earthquake unmanned aerial vehicle (UAV) images. The results of the experiments indicate that this approach can accurately classify buildings with different damage levels. The overall classification accuracy was 94.44%, 85.53%, and 77.49% when the damage to the buildings was divided into two, three, and four categories, respectively.

Dimethyl fumarate improves cognitive impairment by enhancing hippocampal brain-derived neurotrophic factor levels in hypothyroid rats.

BACKGROUND: Dimethyl fumarate (DMF) is an effective drug for multiple sclerosis and can improve the cognitive dysfunction caused by streptozotocin, but the effect on cognitive dysfunction caused by hypothyroidism is unclear. METHODS: After the hypothyroidism rat model induced by propylthiouracil, we gave rats 25 mg/kg DMF by gavage. The body weight during model building and administration was recorded. The levels of T4 and T3 in serum were detected by an automatic biochemical analyzer. Morris water maze test was used to detect the effect of DMF on cognitive learning ability. The effect of DMF on Nissl bodies in the brain tissue was evaluated by Nissl staining. The mRNA and protein levels of BDNF in brain tissue were detected by quantitative reverse transcription-polymerase chain reaction and Western blot. The degrees of p-AKT/AKT and p-CREB/CREB in brain tissue were detected by Western blot. RESULTS: After DMF treatment, the body weight of hypothyroid rats recovered, and the levels of T3 and T4 in the serum were ameliorated. DMF also reduced the escape latency and distance traveled, and increased the swim speed. The number of Nissl bodies and expression of BDNF, p-AKT/AKT, and p-CREB/CREB in the brain tissue were increased after DMF treatment. CONCLUSION: DMF improved the cognitive dysfunction of hypothyroid rats by increasing the level of BDNF in the brain tissue of hypothyroid rats.

Minimalist O2 generator formed by in situ KMnO4 oxidation for tumor cascade therapy.

Diverse oxygen generation strategies have been developed to overcome hypoxia in tumors for enhancing the therapeutic efficacy, but inevitably suffering from tedious synthesis process of oxygen generators in vitro before in vivo administration. Herein, we show direct injection of commercially and clinically used KMnO4 into solid tumors enables in situ formation of MnO2 as an oxygen depot for cascade oxidation damage and enhanced photodynamic therapy. KMnO4 can damage tumor tissues by oxidation and generate MnO2, and subsequent intravenous injection of Ce6 allows MnO2-triggered hypoxia-modulated photodynamic therapy of tumors. Excellent cascade tumor suppression effect is realized both in vitro and in vivo based on the KMnO4-Ce6 system without the need of synthesis. The proposed strategy lays down a novel way with unprecedented superiors of no need of synthesis process and ultra-facile administration procedure for tumor hypoxia-modulated cascade therapy.